Project Summary The goal of P3 is to explore methods for identifying OCD-relevant circuitry in individuals. As targets for invasive and non-invasive OCD treatments become available, a bottleneck for translation in clinical practice is the ability to robustly identify affected circuits in individual patients and measure network modulation. More broadly, focus on groups in neuroimaging studies has slowed translation of findings to the clinical arena where the focus is on the individual. If successful, the project will provide a general set of methods for identifying within-individual network measures that can guide interventions and serve as tailored biomarkers for clinical readouts. The central hypothesis of our Center is that OCD is characterized by hyperconnectivity between the amyg/vmPFC and dACC/ OFC and decreased connectivity between dlPFC/vlPFC and dACC/OFC. This change in balance between emotional processing and cognitive control systems results in a pathological heightened activity state in the dACC/OFC/vlPFC/DS circuitry. In this project we will explore core nodes of this circuitry within individuals and use these methods to explore neuromodulatory effects of OCD circuitry. Aim 1. Identify OCD- relevant circuitry in healthy individuals from the available data including the spatial variability in node location. We hypothesize that, while clustering around the group central tendency, the location of key nodes including the dACC and vlPFC will spatially shift across individuals. These measures will be used to build a variability map. Aim 2. Develop and validate an HCP-inspired connectomic acquisition and analysis strategy targeting diffusion and functional connectivity on a widely available MRI platform. Aim 3. Examine changes in OCD circuitry before and after neuromodulation, 3A. OCD circuitry will be measured in 12 individuals before and after cingulotomy. We hypothesize that coupling between DS and regions just rostral to the cingulotomy will be reduced in effective treatment and preserved in ineffective treatment. 3B. A within-subject TMS study motivated by P4 will analyze before vs after TMS stimulation to further explore whether connectivity measures can be used as a readout of circuit-level perturbations in the individual.